The beta adrenergic receptors (betaAR) comprise one of the most studied families of G protein coupled receptors (GPCRs), and beta agonists and antagonists are commonly used in clinical pharmacology. Despite this cornucopia of scientific knowledge and clinical experience, comparatively little is know about betaARs and pain. The literature suggests contrasting views on the role of betaARs in pain. In some experimental conditions the activation of the receptor is pronociceptive and under other conditions it is anti-nociceptive leaving the role of the betaARs in pain uncertain. The mechanism of action of the effects of the betaARs on peripheral nociceptors have yet to be fully characterized and this represents an important gap in knowledge. In this application, we propose to test the central hypothesis that beta1 adrenergic receptor activation inhibits trigeminal nociceptors via a direct mechanism of action. Our preliminary results indicate that the mRNA encoding the beta1AR and identified beta1 receptor binding sites are present at greater levels in trigeminal ganglia (TGG) neurons than the beta2 receptor. In addition, application of a beta1 agonist inhibits release of iCGRP when stimulated with BK/PGE2. These preliminary data are consistent with the hypothesis that betaARs agonists inhibit nociceptors via activation of a beta1 adrenergic receptor mechanism.